Abstract
Background. In January 2021, the European Union ended the license of Mancozeb, the bestselling ethylenedithiocarbamate (EBDC) fungicide, because of some properties typical of human carcinogens. This decision contrasts the IARC classification of EBDC fungicides (Group 3, not classifiable as to human carcinogenicity). A systematic review of the scientific literature was conducted to explore the current evidence. Methods. Human and experimental studies of cancer and exposure to EBDC fungicides (Mancozeb, Maneb, Zineb, and others) and ethylene thiourea (ETU), their major metabolite, published in English as of December 2021, were retrieved using PubMed, the list of references of the relevant reports, and grey literature. Results. The epidemiological evidence of EBDC carcinogenicity is inadequate, with two studies each suggesting an association with melanoma and brain cancer and inconsistent findings for thyroid cancer. Experimental animal studies point at thyroid cancer in rats and liver cancer in mice, while multiple organs were affected following the long-term oral administration of Mancozeb. The mechanism of thyroid carcinogenesis in rats has also been shown to occur in humans. Genotoxic effects have been reported. Conclusions. The results of this systematic review suggest inadequate evidence for the carcinogenicity of EBDC fungicides from human studies and sufficient evidence from animal studies, with positive results on three out of ten key characteristics of carcinogens applying to humans as well. An IARC re-evaluation of the human carcinogenicity of EBDC fungicides is warranted.
Highlights
The results of this systematic review suggest inadequate evidence for the carcinogenicity of EBDC fungicides from human studies and sufficient evidence from animal studies, with positive results on three out of ten key characteristics of carcinogens applying to humans as well
The European Commission banned the use of Mancozeb, the bestselling ethylenedithiocarbamate (EBDC) fungicide, from February 2021
Monograph N. 79 downgraded ethylene thiourea (ETU) from group 2B to Group 3 of human carcinogens [1]. Such a decision referred to the industrial uses of ETU as an accelerator for the vulcanization of polychloroprene and other rubbers, to its occurrence as an impurity in preparations of EBDC fungicides, and to its internal exposure as a product of EBDC metabolism. Such decision underwent criticism [2] based on animal studies suggesting a goitrogenic effect and a link with thyroid cancer and a report showing increased TSH levels and genetic damage in agricultural workers exposed to EBDCs [3]
Summary
The European Commission banned the use of Mancozeb, the bestselling ethylenedithiocarbamate (EBDC) fungicide, from February 2021. Such a decision referred to the industrial uses of ETU as an accelerator for the vulcanization of polychloroprene and other rubbers, to its occurrence as an impurity in preparations of EBDC fungicides, and to its internal exposure as a product of EBDC metabolism Such decision underwent criticism [2] based on animal studies suggesting a goitrogenic effect and a link with thyroid cancer and a report showing increased TSH levels and genetic damage in agricultural workers exposed to EBDCs [3]. In their reply against the criticism, two members of the IARC Monograph No 79 Working Group stressed two points [4]:. An IARC re-evaluation of the human carcinogenicity of EBDC fungicides is warranted
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